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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #340965
Title: Adiponectin, insulin sensitivity, beta-cell function, and racial/ethnic disparity in treatment failure rates in TODAY

Author
item ARSLANIAN, SILVA - University Of Pittsburgh Medical Center
item EL GHORMLI, L - George Washington University
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item CAPRIO, S - Yale School Of Medicine
item GOLAND, R - Columbia University - New York
item HAYMOND, MOREY - Children'S Nutrition Research Center (CNRC)
item LEVITSKY, L - Massachusetts General Hospital
item NADEAU, K - University Of Colorado
item WHITE, N - Washington University
item WILLI, S - The Children'S Hospital Of Philadelphia

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/3/2016
Publication Date: 11/1/2016
Citation: Arslanian, S., El Ghormli, L., Bacha, F., Caprio, S., Goland, R., Haymond, M.W., Levitsky, L., Nadeau, K.J., White, N.H., Willi, S.M. 2016. Adiponectin, insulin sensitivity, beta-cell function, and racial/ethnic disparity in treatment failure rates in TODAY. Diabetes Care. 40(1):85-93.

Interpretive Summary: There are racial differences in the response to different therapies for type 2 diabetes in youth, with greater failure rates in non-Hispanic Blacks (NHB) in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. We investigated potential reasons for the greater failure rates by ethnic group. We studied measures of insulin sensitivity, insulin secretion and adiponectin among the 3 different racial groups in TODAY. We found that NHB had significantly lower adiponectin than the 2 other racial groups and exhibited a significantly smaller increase in adiponectin in response to therapy. Adiponectin levels were significantly lower in individuals who were more likely not to respond to different therapies for type 2 diabetes. We conclude that adiponectin is a reliable biomarker of treatment response in youth with type 2 diabetes. The lower treatment-associated increase in adiponectin in NH Blacks (about 50% lower) compared with NH Whites and Hispanics may explain the racial/ethnic disparity with higher treatment failure rates in NH Blacks in TODAY.

Technical Abstract: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated that glycemic failure rates in the three treatments combined – metformin plus rosiglitazone, metformin alone, and metformin plus lifestyle – were higher in non-Hispanic blacks (NHB; 52.8%) versus non-Hispanic whites (NHW; 36.6%) and Hispanics (H; 45.0%). Moreover, metformin alone was less effective in NHB versus NHW versus H youth. This study describes treatment-associated changes in adiponectin, insulin sensitivity, and beta-cell function over time among the three racial/ethnic groups to understand potential mechanism(s) responsible for this racial/ethnic disparity. TODAY participants underwent periodic oral glucose tolerance tests to determine insulin sensitivity, C-peptide index, and oral disposition index (oDI), with measurements of total and high-molecular-weight adiponectin (HMWA). At baseline NHB had significantly lower HMWA than NHW and H and exhibited a significantly smaller increase (17.3% vs. 33.7% vs. 29.9%, respectively) during the first 6 months overall. Increases in HMWA were associated with reductions in glycemic failure in the three racial/ethnic groups combined (hazard ratio 0.61, P<0.0001) and in each race/ethnicity separately. Over time, HMWA was significantly lower in those who failed versus did not fail treatment, irrespective of race/ethnicity. There were no differences in treatment-associated temporal changes in insulin sensitivity, C-peptide index, and oDI among the three racial/ethnic groups. HMWA is a reliable biomarker of treatment response in youth with type 2 diabetes. The diminutive treatment-associated increase in HMWA in NHB (~50% lower) compared with NHW and H may explain the observed racial/ethnic disparity with higher therapeutic failure rates in NHB in TODAY.